Biological buffered saline solution as solvent in agar-carbomer hydrogel synthesis

The role of phosphate buffer saline solution (PBS) was investigated here as a solvent in the polycondensation synthesis of an injectable agar-carbomer based hydrogel, a promising new material specifically intended for regenerative medicine applications. The effects of PBS, with respect to standard distilled water (DW), were quantitatively assessed. Experiments were performed both from physico-chemical and biological points of view. Titration showed higher stability due to the presence of the buffer solution; ESEM analysis confirmed its distribution along the polymeric fibers and infrared spectroscopy showed the consequent anionic nature of the polymeric network. This electrostatic nature of the matrix was confirmed by mass equilibrium swelling data performed at different pH values of the swelling medium. A very relevant role of the solvent was observed also with respect to cell housing inside such hydrogels: living cell counts showed a high amount of cells surviving the latency period of encapsulation in hydrogel when PBS was applied while only very few survived in a deionized water based gel. Obtained data allowed a novel understanding of the causeeffect cascades of all observed phenomena which suggest the PBS fundamental role both in fine control of hydrogel preparation and in material tuning according to the specific needs of different target tissues; the latter being a feature of primary importance when applying hydrogels as cell carriers in regenerative medicine applications.     

Drug–Polymer Interactions in Hydrogel‐based Drug‐Delivery Systems: An Experimental and Theoretical Study

In drug‐delivery systems, drug transport is a key step, but the interpretation of the transport mechanism is still controversial. Here, we investigated a promising hydrogel library loaded with the anticonvulsant drug ethosuximide (ESM). The self‐diffusion coefficient of ESM was measured using two methods: a direct and advanced measurement with a pulsed field gradient spin‐echo (PFGSE) method, using an NMR spectrometer equipped with high‐resolution magic angle spinning (HR‐MAS) probe, and an indirect one based on fitting in vitro drug‐delivery data. Starting from the experimental data a mathematical model without fitted parameters was developed and all the phenomena involved, that is, adsorption and diffusion, were considered. At low drug concentrations, adsorption prevails and consequently the diffusivity in the gels is lower than that in water. At high drug concentrations, where all adsorption sites are saturated, the diffusion in the gels is similar to that in a water solution. This study may pave the way for better device design.     

Novel Highly Active Niobium Catalysts for Ring Opening Metathesis Polymerization of Norbornene

Ring‐opening metathesis polymerization (ROMP) of norbornene catalyzed by niobium(V) N,N‐dialkylcarbamates Nb(O₂CNR₂)₅, R = Et ( 1 ), Me ( 2 ) was studied in the presence of methylaluminoxane (MAO) as a cocatalyst. These novel catalytic systems resulted very active in chlorobenzene: 1 in the presence of methylaluminoxane catalyzes the ROMP of norbornene with the highest activity (29 000 kg of polymer/mol of catalyst × hour) never reported up to now for niobium catalysts. The high productivity appears particularly attractive considering that these precursors are rather cheap and easy to synthesize and to handle. Polynorbornenes were characterized by FT‐IR and NMR spectroscopies and by DSC calorimetry. A new FT‐IR method for the swift determination of the cis/trans content of the polymer is presented.

     

Combining Topological and Steric Constraints for the Preparation of Heteroleptic Copper(I) Complexes

Heteroleptic copper(I) complexes have been prepared from a macrocyclic ligand incorporating a 2,9‐diphenyl‐1,10‐phenanthroline subunit ( M30 ) and two bis‐phosphines, namely bis[(2‐diphenylphosphino)phenyl] ether (POP) and 1,3‐bis(diphenylphosphino)propane (dppp). In both cases, the diphenylphosphino moieties of the PP ligand are too bulky to pass through the 30‐membered ring of M30 during the coordination process, hence the formation of C_2v‐symmetrical pseudo‐rotaxanes is prevented. When POP is used, X‐ray crystal structure analysis shows the formation of a highly distorted [Cu( M30 )(POP)]⁺ complex in which the POP ligand is only partially threaded through the M30 unit. This compound is poorly stable as the Cu^I cation is not in a favorable coordination environment due to steric constraints. By contrast, in the case of dppp, the bis‐phosphine ligand undergoes both steric and topological constraints and adopts a nonchelating coordination mode to generate [Cu₂( M30 )₂(μ‐dppp)](BF₄)₂. This compound exhibits metal‐to‐ligand charge transfer (MLCT) emission characterized by a very large Stokes’ shift (≈200 nm) that is not attributed to a dramatic structural distortion between the ground and the emitting states but to very weak MLCT absorption transitions at longer wavelengths. Accordingly, [Cu₂( M30 )₂(μ‐dppp)](BF₄)₂ shows unusually high luminescence quantum yields for Cu^I complexes, both in solution and in the solid state (0.5 and 7 %, respectively).     

Ligand-Free Pd-Catalyzed Reductive Mizoroki-Heck Reaction Strategy for the One-Pot Synthesis of Functionalized Oxygen Heterocycles in Deep Eutectic Solvents

A Deep Eutectic Solvent, choline chloride/glycerol (1 : 2 mol mol⁻¹), proved to be an effective and sustainable reaction medium to promote telescoped, one-pot Mizoroki-Heck cross-coupling/reduction processes between 2,3-dihydrofuran or 3,4-dihydro-2H-pyran and several (hetero)aryl halides to easily access valuable 2-(hetero)aryl tetrahydrofuran (THF) or tetrahydropyran derivatives in up to 95 % yield. Notably, the whole transformation takes place under aerobic conditions, in the absence of additional ligands, and with a good substrate scope. The practicability of the method is also exemplified by the sustainable synthesis of two key THF derivatives, which are side chains of pharmacologically relevant inhibitors of Kv1.2 channel.     

Effects of inhibitors of Delta24(25)-sterol methyl transferase on the ultrastructure of epimastigotes of Trypanosoma cruzi.

Trypanosoma cruzi is the ethiological agent of Chagas disease. New compounds are being developed based on the biosynthesis and function of sterols, because T. cruzi has a requirement for specific endogenous sterols for growth and survival. Sterol biosynthesis inhibitors (SBIs) are drugs commonly used against fungal diseases. These drugs act by depleting essential and specific membrane components and/or inducing the accumulation of toxic intermediary or lateral products of the biosynthetic pathway. In this work we present the effects of WSP488, WSP501, and WSP561, specific inhibitors of Delta24(25)-sterol methyl transferase, on the ultrastructure of T. cruzi epimastigotes. All three drugs inhibited parasite multiplication at low concentrations, with IC50 values of 0.48, 0.44, and 0.48 muM, respectively, and induced marked morphological changes including (a) blockage of cell division; (b) swelling of the mitochondrion, with several projections and depressions; (c) swelling of the perinuclear space; (d) presence of autophagosomes and myelin-like figures; (e) enlargement of the flagellar pocket and of a cytoplasmic vacuole located in close association with the flagellar pocket; (f) detachment of the membrane of the cell body; and (g) formation of a vesicle at the surface of the parasite between the flagellar pocket and the cytostome. Our results show that these drugs are potent in vitro inhibitors of growth of T. cruzi.     

Influence of Freezing and Different Drying Methods on Volatile Profiles of Strawberry and Analysis of Volatile Compounds of Strawberry Commercial Jams

Strawberry is the most consumed berry fruit worldwide due to its unique aroma and flavor. Drying fruits to produce a powder represents one of the possible conservation methods to extend their shelf-life. The aim of the present study was to compare the influence of freezing and different drying methods on the volatile profile of strawberry using the HS-SPME/GC–MS method, in addition to analysis of strawberry jam volatiles. A total of 165 compounds were identified, accounting for 85.03–96.88% of the total volatile compositions. Results and PCA showed that freezing and each drying process affected the volatile profile in a different way, and the most remarkable representative differential volatiles were ethyl hexanoate, hexyl acetate, (E)-2-hexenyl acetate, mesifurane, (E)-nerolidol, γ-decalactone, 1-hexanol, and acetoin. Shade air-dried, frozen, freeze-dried, and oven-dried 45 °C samples retained more of the fruity and sweet aromas of strawberry, representing more than 68% of the total aroma intensity according to the literature. In contrast, the microwave-drying method showed drastic loss of fruity esters. Strawberry jams demonstrated complete destruction of esters and alcohols in most jams, while terpenes were significantly increased. These findings help better understand the aroma of strawberry and provide a guide for the effects of drying, freezing, and jam processing.     

Chemical Identification of Specialized Metabolites from Sulla (Hedysarum coronarium L.) Collected in Southern Italy

Sulla (Hedysarum coronarium L.) is a biennal forage legume originated from the Mediterranean basin and used for animal feeding due to its high forage quality and palatability. Several species of Hedysarum have been considered for their nutritional, pharmaceutical, and biological properties, and different applications have been reported, both for human consumption and animal nutrition. Although a systematic investigation of the chemical constituents of Hedysarum spp. has been performed in order to provide chemotaxonomic evidences for the genus and to support the pharmacological application of several species within the genus, few data are available on the chemical constituents of H. coronarium, and only the content of condensed tannins and flavonoids in leaves has been previously reported. In the present paper, results from a detailed chemical analysis of the extracts from the leaves and flowers of H. coronarium grown wild in southern Italy are presented. Identification of the main specialized metabolites within the chemical classes of flavonoids, proanthocyanidins and saponins, is described, including considerations on their content in the two plant organs. Information acquired from this study expands the knowledge on H. coronarium as a source of valuable phytochemicals for different applications in human and animal health and nutrition.     

Pyrolysis Kinetics and Flammability Evaluation of Rigid Polyurethane with Different Isocyanate Content

Polyurethane (PU) is a typical product of the reaction between isocyanate and polyol, whose ratio would greatly influence material properties. In this paper, to investigate the influence of isocyanate on PU thermal stability and flammability, three kinds of rigid polyurethanes (RPUs) with different isocyanate ratio (1.05, 1.1, and 2.0) were manufactured in a laboratory and employed to have a series of TG (thermogravimetry), DSC (differential scanning calorimetry), and cone calorimetry tests. Kissinger’s method was used to calculate the activation energy and judge their stabilities. However, for such a complex degradation which consists of five reactions, it does not make sense by Kissinger method to obtain only two peak active energies. Considering complexity of PU degradation in air, genetic algorithm (GA) was employed to calculate kinetic triplets of five sub-reactions. The effects of isocyanate contents on each sub-reaction stability were obtained and then analyzed. By cone calorimeter testing, we found that great differences in heat release rate data. However, DSC analysis showed a complete opposite changed trend. Such difference is caused by DSC and calorimeter’s sample morphology, the former using grinded polyurethane powders but the latter polyurethane foam block.